Department of Clinical Laboratory, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang City, Guizhou, China.
School of Life Science and Technology, School of Engineering, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.
Environ Toxicol. 2024 Mar;39(3):1505-1520. doi: 10.1002/tox.24050. Epub 2023 Nov 23.
Cytochrome P450 (CYP) 4Z1 (CYP4Z1) has recently garnered much interest as its expression predicts a poor prognosis and as a oncogene in breast cancer, and overexpressed in other many cancers. We previously showed that CYP4Z1 acts as a promoter of cancer stem cells (CSCs) to facilitate the occurrence and development of breast cancer. Here, RNA sequencing found that 1-benzylimidazole (1-Benzy) held a preferable correlation with breast cancer and suppressed the expression of CSC makers. Further functional experiments, including mammary spheroid formation, wound-healing, transwell-invasion, detection of tumor initiation, and metastatic ability, showed that 1-Benzy suppressed the stemness and metastasis of breast cancer cells. Additionally, we further demonstrated that CYP4Z1 is necessary for 1-Benzy-mediated suppression on breast cancer stemness and 1-Benzy exerted a weaker effect in breast cancer cells with CYP4Z1 knockdown. Taken together, our data suggest that 1-Benzy might be a potential drug suppressing breast cancer stemness via targeting CYP4Z1.
细胞色素 P450（CYP）4Z1（CYP4Z1）最近备受关注，因为其表达预示着不良预后，并且是乳腺癌中的癌基因，在许多其他癌症中过表达。我们之前表明，CYP4Z1 作为癌症干细胞（CSC）的促进剂，促进乳腺癌的发生和发展。在这里，RNA 测序发现 1-苯甲基咪唑（1-Benzy）与乳腺癌具有更好的相关性，并抑制了 CSC 标志物的表达。进一步的功能实验，包括乳腺球体形成、划痕愈合、Transwell 侵袭、肿瘤起始检测和转移能力检测，表明 1-Benzy 抑制了乳腺癌细胞的干性和转移。此外，我们进一步证明 CYP4Z1 是 1-Benzy 介导的对乳腺癌干细胞干性抑制所必需的，并且在 CYP4Z1 敲低的乳腺癌细胞中，1-Benzy 发挥的作用较弱。综上所述，我们的数据表明，1-Benzy 可能是一种通过靶向 CYP4Z1 抑制乳腺癌干细胞干性的潜在药物。
